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靶向头颈部肿瘤干细胞:从生物学层面到治疗前景

Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives.

作者信息

Méry Benoîte, Guy Jean-Baptiste, Espenel Sophie, Wozny Anne-Sophie, Simonet Stéphanie, Vallard Alexis, Alphonse Gersende, Ardail Dominique, Rodriguez-Lafrasse Claire, Magné Nicolas

机构信息

Benoîte Méry, Jean-Baptiste Guy, Sophie Espenel, Alexis Vallard, Nicolas Magné, Department of Radiotherapy, Lucien Neuwirth Cancer Institute, 42271 Saint-Priest en Jarez, France.

出版信息

World J Stem Cells. 2016 Jan 26;8(1):13-21. doi: 10.4252/wjsc.v8.i1.13.

Abstract

Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

摘要

头颈部鳞状细胞癌(HNSCC)是全球第六大常见癌症。手术、放疗、化疗以及各种方法的联合等有效治疗方式被用于该疾病的管理。在大多数情况下,治疗无法实现癌症的完全治愈。近年来,治疗失败的关键决定因素之一似乎是存在逃避现有疗法的癌症干细胞(CSC)。CSC在肿瘤总负荷中占比很小,但在决定治疗结果方面可能发挥着 disproportionately 重要的作用。CSC具有自我更新、高迁移能力、耐药性、高增殖能力等干细胞特征。大量证据表明,CSC对放疗和化疗具有特别的抗性。在HNSCC中,越来越多的证据表明CSC在肿瘤起始、疾病进展、转移和治疗抗性中起着不可或缺的作用。鉴于这些观察结果,本综述总结了HNSCC中CSC的生物学特性,概述了成功根除HNSCC中CSC的靶向策略,包括靶向自我更新控制途径、阻断上皮间质转化、靶向微环境、免疫治疗方法,并强调了为开发新的治疗方式而更好地理解CSC生物学的必要性。

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